Correction to: MEAM-based MD calculations of melting temperature for Fe.

A Correction to this paper has been published: https://doi.org/10.1007/s00894-020-04609-9.

Development of an Optimized MALDI-TOF-MS Method for High-Throughput Identification of High-Molecular-Weight Glutenin Subunits in Wheat.

Because high-molecular-weight glutenin subunits (HMW-GS) are important contributors to wheat end-use quality, there is a need for high-throughput identification of HMW-GS in wheat genetic resources and breeding lines. We developed an optimized method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to distinguish individual HMW-GS by considering the effects of the alkylating reagent in protein extraction, solvent components, dissolving volume, and matrix II components. Using the optimized method, 18 of 22 HMW-GS were successfully identified in standard wheat cultivars by differences in molecular weights or by their associations with other tightly linked subunits. Interestingly, 1Bx7 subunits were divided into 1Bx7 group 1 and 1Bx7 group 2 proteins with molecular weights of about 82,400 and 83,000 Da, respectively. Cultivars containing the 1Bx7 group 2 proteins were distinguished from those containing 1Bx7OE using well-known DNA markers. HMW-GS 1Ax2* and 1Bx6 and 1By8 and 1By8*, which are difficult to distinguish due to very similar molecular weights, were easily identified using RP-HPLC. To validate the method, HMW-GS from 38 Korean wheat varieties previously evaluated by SDS-PAGE combined with RP-HPLC were analyzed by MALDI-TOF-MS. The optimized MALDI-TOF-MS method will be a rapid, high-throughput tool for selecting lines containing desirable HMW-GS for breeding efforts.

Upregulation of the MYB2 Transcription Factor Is Associated with Increased Accumulation of Anthocyanin in the Leaves of Dendrobium bigibbum.

Orchids with colorful leaves and flowers have significant ornamental value. Here, we used γ-irradiation-based mutagenesis to produce a Dendrobium bigibbum mutant that developed purple instead of the normal green leaves. RNA sequencing of the mutant plant identified 2513 differentially expressed genes, including 1870 up- and 706 downregulated genes. The purple leaf color of mutant leaves was associated with increased expression of genes that encoded key biosynthetic enzymes in the anthocyanin biosynthetic pathway. In addition, the mutant leaves also showed increased expression of several families of transcription factors including the MYB2 gene. Transient overexpression of D. biggibumMYB2 in Nicotiana benthamiana was associated with increased expression of endogenous anthocyanin biosynthesis genes. Interestingly, transient overexpression of orthologous MYB2 genes from other orchids did not upregulate expression of endogenous anthocyanin biosynthesis genes. Together, these results suggest that the purple coloration of D. biggibum leaves is at least associated with increased expression of the MYB2 gene, and the MYB2 orthologs from orchids likely function differently, regardless of their high level of similarity.

MEAM-based MD calculations of melting temperature for Fe.

The molecular dynamics (MD) simulations were applied to the melting transition of the BCC metal Fe using the modified embedded atom method (MEAM) potential proposed by Jin et al. [Appl. Phys. A120 (2015) 189], and the newly derived formulas were adopted to calculate the forces acting on atoms in the MD simulations. We first determined the structural and energetic properties of the effectively infinite solid with no boundaries, and then investigated the Fe samples with low-index surfaces, namely Fe(100), Fe(110), and Fe(111). The simulations show that as the temperature increases, the (111) surface firstly disorders, followed by the (100) surface, while the (110) surface remains stable up to the melting temperature. The disorder phenomenon diffuses from the surface to the entire block, and as the density of atoms on the surface decreases, the effect of the premelting phenomenon also increases, being most pronounced on Fe(111) which has the lowest surface density. This conclusion is in line with the behavior found for BCC metal V in the previous simulation study.

Frequency, Spectrum, and Stability of Leaf Mutants Induced by Diverse γ-Ray Treatments in Two Cymbidium Hybrids.

Ionizing radiation combined with in vitro tissue culture has been used for development of new cultivars in diverse crops. The effects of ionizing radiation on mutation induction have been analyzed on several orchid species, including Cymbidium. Limited information is available on the comparison of mutation frequency and spectrum based on phenotypes in Cymbidium species. In addition, the stability of induced chimera mutants in Cymbidium is unknown. In this study, we analyzed the radiation sensitivity, mutation frequency, and spectrum of mutants induced by diverse γ-ray treatments, and analyzed the stability of induced chimera mutants in the Cymbidium hybrid cultivars RB003 and RB012. The optimal γ-irradiation conditions of each cultivar differed as follows: RB003, mutation frequency of 4.06% (under 35 Gy/4 h); RB012, 1.51% (20 Gy/1 h). Re-irradiation of γ-rays broadened the mutation spectrum observed in RB012. The stability of leaf-color chimera mutants was higher than that of leaf-shape chimeras, and stability was dependent on the chimera type and location of a mutation in the cell layers of the shoot apical meristem. These results indicated that short-term γ-irradiation was more effective to induce mutations in Cymbidium. Information on the stability of chimera mutants will be useful for mutation breeding of diverse ornamental plants.

Dark/Light Treatments Followed by γ-Irradiation Increase the Frequency of Leaf-Color Mutants in Cymbidium.

Radiation randomly induces chromosomal mutations in plants. However, it was recently found that the frequency of flower-color mutants could be specifically increased by upregulating anthocyanin pathway gene expression before radiation treatments. The mechanisms of chlorophyll biosynthesis and degradation are active areas of plant study because chlorophyll metabolism is closely connected to photosynthesis. In this study, we determined the dark/light treatment conditions that resulted in upregulation of the expression levels of six chlorophyll pathway genes, uroporphyrinogen III synthase (HEMD), uroporphyrinogen III decarboxylase (HEME2), NADPH-protochlorophyllide oxidoreductase (POR) A (PORA), chlorophyll synthase (CHLG), chlorophyllase (CLH2), and red chlorophyll catabolite reductase (RCCR), and measured their effects on the γ-irradiation-induced frequencies of leaf-color mutants in two Cymbidium cultivars. To degrade chlorophyll in rhizomes, 60-75 days of dark treatment were required. To upregulate the expressions of chlorophyll pathway genes, 10 days of light treatment appeared to be optimal. Dark/light treatments followed by γ-irradiation increased chlorophyll-related leaf mutants by 1.4- to 2.0-fold compared with γ-ray treatment alone. Dark/light treatments combined with γ-irradiation increased the frequency of leaf-color mutants in Cymbidium, which supports the wider implementation of a plant breeding methodology that increases the mutation frequency of a target trait by controlling the expression of target trait-related genes.

Transcriptome analysis to identify candidate genes associated with the yellow-leaf phenotype of a Cymbidium mutant generated by γ-irradiation.

Leaf color is an important agronomic trait in flowering plants, including orchids. However, factors underlying leaf phenotypes in plants remain largely unclear. A mutant displaying yellow leaves was obtained by the γ-ray-based mutagenesis of a Cymbidium orchid and characterized using RNA sequencing. A total of 144,918 unigenes obtained from over 25 million reads were assigned to 22 metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes database. In addition, gene ontology was used to classify the predicted functions of transcripts into 73 functional groups. The RNA sequencing analysis identified 2,267 differentially expressed genes between wild-type and mutant Cymbidium sp. Genes involved in the chlorophyll biosynthesis and degradation, as well as ion transport, were identified and assayed for their expression levels in wild-type and mutant plants using quantitative real-time profiling. No critical expression changes were detected in genes involved in chlorophyll biosynthesis. In contrast, seven genes involved in ion transport, including two metal ion transporters, were down-regulated, and chlorophyllase 2, associated with chlorophyll degradation, was up-regulated. Together, these results suggest that alterations in chlorophyll metabolism and/or ion transport might contribute to leaf color in Cymbidium orchids.

Predictive Factors for Efficacy of AST-120 Treatment in Diabetic Nephropathy: a Prospective Single-Arm, Open-Label, Multi-Center Study.

BACKGROUND: Removal of uremic toxins such as indoxyl sulfate by AST-120 is known to improve renal function and delay the initiation of dialysis in patients with advanced chronic kidney disease. However, it is unclear whether the addition of AST-120 to conventional treatments is effective in delaying the progression of renal dysfunction in patients with diabetic nephropathy. METHODS: A total of 100 patients with type 2 diabetes and renal dysfunction (serum creatinine levels ranging from 1.5 to 3.0 mg/dL) were recruited from eight centers in Korea and treated with AST-120 (6 g/day) for 24 weeks. The primary endpoint was improvement in renal function measured as the gradient of the reciprocal serum creatinine level (1/sCr) over time (i.e., the ratio of 1/sCr time slope for post- to pre-AST-120 therapy). A response was defined as a ratio change of the regression coefficient of 1/sCr ≤ 0.90. RESULTS: Renal function improved in 80.3% of patients (61/76) after 24 weeks of AST-120 treatment. There were no differences between responder and non-responder groups in baseline characteristics except for diastolic blood pressure (73.5 ± 9.5 mmHg in the responder group vs. 79.3 ± 11.1 mmHg in the non-responder group; P = 0.046). Serum lipid peroxidation level decreased significantly in the responder group (from 2.25 ± 0.56 µol/L to 1.91 ± 0.72 µol/L; P = 0.002) but not in the non-responder group. CONCLUSION: The addition of AST-120 to conventional treatments may delay the progression of renal dysfunction in diabetic nephropathy. The antioxidant effect of AST-120 might contribute to improvement in renal function.

Midfacial degloving approach for management of the maxillary fibrous dysplasia: a case report.

BACKGROUND: Fibrous dysplasia (FD) is a benign bone lesion characterized by the progressive replacement of normal bone with fibro-osseous connective tissue. The maxilla is the most commonly affected area of facial bone, resulting in facial asymmetry and functional disorders. Surgery is an effective management option and involves removing the diseased bone via an intraoral approach: conservative bone shaving or radical excision and reconstruction. CASE PRESENTATION: This case report describes a monostotic fibrous dysplasia in which the patient's right midface had a prominent appearance. The asymmetric maxillary area was surgically recontoured via the midfacial degloving approach under general anesthesia. Follow-up photography and radiographic imaging after surgery showed the structures were in a stable state without recurrence of the FD lesion. Furthermore, there were no visible scars or functional disability, and the patient reported no postoperative discomfort. CONCLUSIONS: In conclusion, the midfacial degloving approach for treatment of maxillary fibrous dysplasia is a reliable and successful treatment option. Without visible scars and virtually free of postoperative functional disability, this approach offers good exposure of the middle third of the face for treatment of maxillary fibrous dysplasia with excellent cosmetic outcomes.

Conservative surgical treatment for ameloblastoma: a report of three cases.

Ameloblastoma treatment varies based on the clinical, histopathologic, and radiographic characteristics. Aggressive surgical treatments, such as marginal or segmental resection, have traditionally been implemented, but some conservative surgical methods are also being introduced, including decompression, enucleation, or curettage. The aim of the present study was to evaluate the possibility of applying these conservative surgical treatments to ameloblastoma and to analyze the prognosis of the procedures and their healing aspects. Among all patients who visited our clinic (Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gangdong) from 2009 to 2017, three who had undergone conservative surgery were recruited. One of these three patients underwent both excision of the lesion and an iliac bone graft during the same procedure. In the other two patients, due to the size of the lesion, decompression was performed to reduce the size of the lesion, and then conservative surgical treatments followed. As shown in the cases of this study, patients were only treated with conservative surgical methods, such as decompression or enucleation. During the follow-up period, there were no recurrences. In conclusion, the use of conservative surgical treatment in ameloblastoma can be a reliable, safe, and successful method.

Comparison of efficacy and safety between endoscopic submucosal dissection and transanal endoscopic microsurgery for the treatment of rectal tumor.

Background/Aim: To compare the treatment efficacy and safety between endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) for the treatment of rectal epithelial tumors, including large adenoma, cancer, and subepithelial tumors (SET). Patients and Methods: We conducted a retrospective analysis of the medical records of 71 patients with rectal tumors who were treated with ESD (48 patients) or TEM (23 patients) from January 2013 to December 2015. The patient group comprised 56 patients with epithelial tumors and 15 patients with SET. Treatment efficacy such as en bloc resection, procedure time, local recurrence, hospital stay, additional procedure rate, and safety between the treatment groups were evaluated and analyzed. Results: There were no significant differences in tumor size, location, macroscopic appearance, and histological depth between ESD and TEM groups. For ESD compared to TEM in rectal epithelial tumors, en bloc resection rates were 95% vs. 93.7% and R0 resection rates were 92.5% vs. 87.5% (P = 0.617); in rectal SET, en bloc resection rates were 100% vs. 100% and R0 resection rates were 87% vs. 85% (P = 0.91). The procedure time was 71.5 ± 51.3 min vs. 105.6 ± 28.2 min (P = 0.016) for epithelial tumors and 32.13 ± 13.4 min vs. 80.71 ± 18.35 min (P = 0.00) for SET, respectively. Hospital stay was 4.3 ± 1.2 days vs. 5.8 ± 1.8 days (P = 0.001) for epithelial tumors and 4.1 ± 4.1 days vs. 5.5 ± 2 days (P = 0.42) for rectal SET, respectively. There were no significant differences between recurrence rates, additional procedure rates, and complications in the two groups. Conclusions: ESD and TEM are both effective and safe for the treatment of rectal epithelial tumors and SET because of favorable R0 resection rates and recurrence rates. However, the ESD group showed shorter procedure times and hospital stays than the TEM group. Therefore, ESD should be considered more preferentially than TEM in the treatment of large rectal epithelial tumors and SET.

Nonislet Cell Tumor Hypoglycemia in a Patient with Adrenal Cortical Carcinoma.

Nonislet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II), causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient's serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation.

Validation of the 7th AJCC/UICC staging system for gastric cancer and a proposal for a new TNM system based on a prognostic score: a retrospective multicenter study.

PURPOSE: We validate the 7th American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system for gastric cancer and propose a new staging system that reflects the prognostic significances of each of T and N category. METHODS: Data from 5,957 patients who underwent curative gastrectomies from 2000 to 2007 at 4 university hospitals in Daegu Metropolitan city in Korea were analyzed for the validation of the 7th AJCC/UICC staging system for gastric cancer. The hazard ratios of the respective T and N categories were estimated and converted to weightings and summated to make prognostic score (P-score). Homogeneity and stage grouping were determined according to the P-scores. RESULTS: In the 7th AJCC/UICC staging system for gastric cancer, poor discrimination was noted between stages IIB and IIIA (P = 0.152). In addition, heterogeneity in stage IIB (P = 0.021) and a small gap in 5-year survival rates (1.7%) between stages IA and IB were noted. A new proposed staging system was generated on the basis of P-scores and demonstrated more discrimination between stages and more homogeneity within stages. The new staging system reflects the different prognostic impacts of N3a and N3b. CONCLUSION: Several controversial issues of the 7th AJCC/UICC staging system for gastric cancer were reconfirmed in the present analysis. The TNM system based on P-score appears to be more scientifically accurate than the 7th AJCC/UICC staging system for gastric cancer.

Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model.

Absorbable extracellular matrix (ECM) membrane has recently been used as a barrier membrane (BM) in guided tissue regeneration (GTR) and guided bone regeneration (GBR). Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymes in vivo. In a previous study, to delay degradation time, collagen fibers were treated with cross-linking agents. These compounds prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit delayed tissue integration. In addition, the remaining cross-linker could induce inflammation. Here, we attempted to overcome these problems using a natural ECM membrane. The membrane consisted of freshly harvested porcine pericardium that was stripped from cells and immunoreagents by a cleaning process. Acellular porcine pericardium (APP) showed a bilayer structure with a smooth upper surface and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18-0.35 mm) but with excellent mechanical properties. Tensile strength of APP was 14.15 ± 2.24 MPa. In in vivo experiments, APP was transplanted into rabbit tibia. The biocompatible material was retained for up to 3 months without the need for cross-linking. Therefore, we conclude that APP could support osteogenesis as a BM for up to 3 months.

Comparing the Trend of Physical Activity and Caloric Intake between Lipid-Lowering Drug Users and Nonusers among Adults with Dyslipidemia: Korean National Health and Nutrition Examination Surveys (2010-2013).

BACKGROUND: The purpose of this study was to compare the physical activity and caloric intake trends of lipid-lowering drug users with those of non-users among Korean adults with dyslipidemia. METHODS: This study was a repeated cross-sectional study with a nationally representative sample of 2,635 Korean adults with dyslipidemia based on the 2010-2013 Korea National Health and Nutrition Examination Survey. Physical activity was assessed using the International Physical Activity Questionnaire, and caloric intake was estimated through 24-hour dietary recall. All statistical analyses were conducted using IBM SPSS ver. 21.0 (IBM Co., Armonk, NY, USA). The changes in physical activity and caloric intake were investigated for lipid-lowering drug users and non-users using generalized linear models. RESULTS: The proportion of lipid-lowering drug users in the 2010-2013 survey population increased from 3.5% to 5.0% (P<0.001). Among adults of dyslipidemia, total of 1,562 participants (56.6%) reported taking lipid-lowering drugs, and 1,073 (43.4%) reported not taking lipid-lowering drugs. Drug users were more likely to be older and less educated and to have a diagnosis of diabetes, higher body mass index, and lower low density lipoprotein cholesterol level. Physical activity trends were tested separately for the lipid-lowering drug users and non-users, and a significant decrease was found among the drug users during the study period. Physical activity among the drug users in 2013 was 38% lower (1,357.3±382.7 metabolic equivalent [MET]; P for trend=0.002) than in 2010 (2,201.4±442.6 MET). In contrast, there was no statistically significant difference between drug users and non-users in the trend of caloric intake during the same period. CONCLUSION: Physical activity significantly decreased among lipid-lowering drug users between 2010 and 2013, which was not observed among non-users. The importance of physical activity may need to be re-emphasized for lipid-lowering drug users.

Short-term outcomes of immediate breast reconstruction using an implant or tissue expander after mastectomy in breast cancer patients.

BACKGROUND: Mastectomy is an optional surgical management of breast cancer, but it can cause significant adverse reactions. Breast reconstruction is a concern in post-mastectomy recovery. We assessed the oncologic safety and patient satisfaction following immediate breast reconstruction using an implant or tissue expander. METHODS: We retrospectively reviewed all patients who underwent reconstruction with an implant or tissue expander immediately after mastectomy. Seventy-seven patients underwent breast reconstruction at a general hospital breast cancer center from January 2008 to December 2010. Fourteen patients were excluded due to loss at follow-up, so 63 patients were included in this study. Questionnaires were sent to all patients to assess patient satisfaction. RESULTS: Mean age was 44.1 years (range 29-64). After a median follow-up period of 22.4 months, there was 1 case of locoregional recurrence, 1 case of distant metastasis, and an overall breast cancer-specific survival of 100 %. Overall rate of major complications, such as nipple areolar complex (NAC) necrosis and implant removal, was 11.1 % (7 patients). Of the 10 patients who had NAC necrosis, 6 patients improved after observation and 4 patients had NAC excision. Three patients had their implant removed due to severe infection, leakage, and dissatisfaction, respectively. There were 32 cases of total mastectomy (TM), 12 cases of skin-sparing mastectomy (SSM), and 19 cases of NAC-sparing mastectomy (NSM). According to the questionnaire, 84.1 % were satisfied with the general operational result and 77.8 % with the cosmetic result. Of the 31 patients who received conservative surgery, 87.1 % were satisfied with the general result and 83.9 % with the cosmetic result. CONCLUSIONS: Immediate breast reconstruction using an implant after mastectomy was technically feasible and oncologically safe. In addition, the reconstruction resulted in a relatively high rate of patient satisfaction. Further long-term studies are warranted to confirm these findings.

Medical Manuscript: Serum Total Testosterone as a Prognostic Indicator in Male Patients With Terminal Cancer.

The role of total serum testosterone in the prognosis of terminal cancer is unclear. We retrospectively investigated the total serum testosterone level in 69 male patients with terminal cancer in a palliative care unit. The association between the serum testosterone level and survival was assessed using Cox proportional hazard model. The median value of serum total testosterone was 44.5 ng/dL, far lower than previously reported in patients with advanced cancer. Multivariate analysis revealed thrombocytopenia (adjusted hazard ratio [aHR], 2.68), hypoalbuminemia (aHR, 2.02), azotemia (aHR, 2.67), and lower serum testosterone level (aHR, 2.03) were significantly negatively prognostic of survival. Lower serum testosterone level was an independent unfavorable prognostic factor for life expectancy in male patients with terminal cancer.

Coexistence of gastrointestinal stromal tumor and inflammatory myofibroblastic tumor of the stomach presenting as a collision tumor: first case report and literature review.

Collision tumors of the stomach are rare. We report on a case of a collision tumor consisting of a gastrointestinal stromal tumor (GIST) and an inflammatory myofibroblastic tumor (IMT) of the stomach in a 16-year-old female. A polypoid mass located in the distal body of the stomach was observed on abdominal computed tomography. Laparoscopic wedge resection of the stomach and 4d lymph node biopsy was performed. On gross examination, a protruding submucosal mass, measuring 4 × 3.5 × 2.5 cm in size, was detected. Histological examination showed two distinct GIST and IMT component presenting a collision tumor. The small nodular area, composed of CD117-positive spindle cells, was typical of GIST, and the adjacent larger area, composed of myofibroblastic spindle cells with prominent chronic inflammatory cells infiltrate, mainly lymphocytes and plasma cells, had a characteristic appearance of IMT. The 4d lymph node showed metastatic inflammatory myofibroblastic tumor. To the best of our knowledge, this is the first case of a collision tumor consisting of a GIST and an IMT arising in the stomach.

Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors.

A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-α release assay.

High-yield production of biosugars from Gracilaria verrucosa by acid and enzymatic hydrolysis processes.

Gracilaria verrucosa, the red alga, is a suitable feedstock for biosugar production. This study analyzes biosugar production by the hydrolysis of G. verrucosa conducted under various conditions (i.e., various acid concentrations, substrate concentrations, reaction times, and enzyme dosages). The acid hydrolysates of G. verrucosa yielded a total of 7.47g/L (37.4%) and 10.63g/L (21.26%) of reducing sugars under optimal small (30mL) and large laboratory-scale (1L) hydrolysis processes, respectively. Reducing sugar obtained from acid and enzymatic hydrolysates were 10% higher, with minimum by-products, than those reported in other studies. The mass balance for the small laboratory-scale process showed that the acid and enzymatic hydrolysates had a carbohydrate conversion of 57.2%. The mass balance approach to the entire hydrolysis process of red seaweed for biosugar production can be applied to other saccharification processes.